Selective effects of inhaled methacholine on 3rd generation bronchial blood flow and airway dimensions in awake sheep

Abstract

Evolution and natural selection in mammals has ensured mechanisms for preventing absorption of inhaled molecules from lung airways. The postulate that inhaled cholinergic compounds selectively access airway wall structures was examined in six sheep instrumented at left thoracotomy under general anaesthesia (i.v. propofol 5 mg.kg−1, 3% isoflurane‐oxygen) each with pulsed‐ Doppler blood flow transducers mounted on bronchial artery, and sonomicrometer probes (Bishop et al, Pulm Pharmacol Ther 20, 178–189, 2007) on high air‐flow resistance 3rd generation lingular lobe bronchus. Continuous measurements of bronchial blood flow (Qbr) and conductance (Cbr), plus bronchial hemi‐circumference (CIRCbr) and wall thickness (THbr) were made in recovered, standing, awake sheep. Dose‐response studies were performed using i.v. methacholine (MCh: 0.125–2.0 μg.kg−1), or nebulised MCh (1–32 mg.kg−1) inhaled by mask. MCh i.v. at the highest dose caused 233% rise in Qbr (P< 0.05), and 286% in Cbr (P< 0.05). CIRCbr fell to 90% of control (P< 0.05); THbr did not change. Inhaled MCh at highest dose caused rise in ventilation, and proportional rise in aortic pressure and Qbr; CIRCbr fell to 91% (P< 0.05); Cbr and THbr did not change. Thus cholinoceptor agonists penetrate the airway wall ex‐ or endogenously to maximally contract the bronchial wall, but by unknown selective mechanisms do not penetrate the systemic vascular bed.